Chronic pancreatitis (CP) is a pancreatic disease with poor prognosis characterized clinically by abdominal pain, morphologically by pancreatic stones/calcification, duct dilatation and atrophy, and functionally by pancreatic exocrine and endocrine insufficiency. CP is also known as a risk factor for the development of pancreatic cancer. CP has long been understood based on a fixed disease concept deduced from the clinical and morphological features of the end-stage disease. However, identification of causal genes for hereditary pancreatitis and success in the isolation and culture of pancreatic stellate cells have advanced the understanding of the underlying pathological mechanisms, the early-stage pathophysiology, and the mechanisms behind pancreatic fibrosis. These advances have led to moves aimed at improving patient prognosis through prevention of disease progression by early diagnosis and early therapeutic intervention. The strategy for preventing disease progression has included a proposal for diagnostic criteria for early CP and introduction of a new definition of CP in consideration of the pathological mechanisms. Our group has been committed deeply to these studies and has provided a large amount of information to the world.
Invited Review for the 100th Anniversary of the TJEM
Many studies have consistently reported the bidirectional relationship between problem drinking and psychological distress following a disaster, but the risk factors of problem drinking following a disaster remain unclear. In this study, we therefore aimed to explore the risk factors associated with the incidence of problem drinking among evacuees after the Great East Japan Earthquake of March 11, 2011. We used the data for evacuees of the Fukushima Daiichi nuclear power plant accident, obtained from the Mental Health and Lifestyle Survey. A total of 12,490 individuals from 13 municipalities, which included the evacuation order areas after the accident, completed surveys between 2012 and 2013. The CAGE (Cutting down, Annoyed by criticism, Guilty feeling, and Eye-opener) questionnaire was used to screen the participants for alcohol dependence, and a score ≥ 2 indicated problem drinking. Logistic regression models were applied to investigate the possible predictors of problem drinking. The results showed that insufficient sleep and heavy drinking (≥ 4 drinks per day) were significant risk factors for the incidence of problem drinking in both men and women. Additional risk factors included family financial issues due to the disaster and trauma symptoms among men and a diagnosed history of mental illness among women. Other remaining variables were not significantly associated with problem drinking. The present study is the first to identify the risk factors for problem drinking following a compound disaster. Our findings could be used to develop a primary intervention program to improve evacuees’ health and lives following a disaster.
In contrast to input evaluation (education delivered at school) and output evaluation (students’ capability at graduation), the methods of outcome evaluation (performance after graduation) of medical education have not been sufficiently established. To establish a method to measure the quality of patient care and conduct outcome evaluation, we have been developing a peer review system of medical records. Here, we undertook a pilot study to evaluate the criterion validity of our system by using “evaluation by program directors (supervisors in the hospitals)” as a criterion standard. We selected 13 senior residents from three teaching hospitals. Five reviewers (general internists working in other hospitals) visited the hospitals independently and evaluated five patients’ records for each resident based on the previously established sheet comprising 15 items. Independently, program directors of the senior residents evaluated their clinical performance using an evaluation sheet comprising ten items. Pearson’s analysis revealed statistically significant correlation coefficients in three pairs of assessments including clinical reasoning (r = 0.5848, P = 0.0358). Bootstrap analysis revealed statistically significant correlation coefficients in additional 5 pairs including history taking (r = 0.509, 95% confidence interval: 0.034-0.847). In contrast, the correlation coefficients were low in some items: r = 0.132 (–0.393-0.639) for physical examination and r = 0.089 (–0.847-0.472) for attitude toward patients. To the best of our knowledge, this is the first study, albeit a pilot one, that investigates the criterion validity of medical record evaluations conducted by comparing the assessments of medical records with those by program directors.
After the Fukushima nuclear accident in 2011, there was confusion among the public caused by uncoordinated information about radiation provided by diverse channels. We explored the association between information sources regarding reconstruction progress after the disaster and mental fatigue in Fukushima. We used data from the annual public opinion survey by the Fukushima Prefectural Government on its policies from 2013 to 2015, which contained survey responses from 1,300 community residents randomly selected from the 28 municipalities in the Fukushima Prefecture. The survey contained a question assessing mental fatigue: “How often do you usually feel mentally tired or depressed?” In total, 2,130 participants (758 participants in 2013, 699 participants in 2014, and 673 participants in 2015) were analyzed. The respondents were classified as two categories, “high mental fatigue” and “low mental fatigue,” based on their responses to this question. Overall, the proportion of participants with high mental fatigue was 13.2%. There was no association between the year of survey or occupation and high mental fatigue. Cluster analysis was performed to classify information sources. Then, we conducted a cross-sectional analysis of the associations between clusters of information sources and high mental fatigue. We found that unreliable information sources, such as “Internet” and “a combination of TV, radio, and word of mouth,” were significantly associated with high mental fatigue, compared with reliable information sources, such as “municipal public relations in addition to major media (newspaper, TV, and radio).” These findings provide important insights into how information sources affect mental fatigue following a disaster.
Lamotrigine, a frequently used antiepileptic drug, inhibits voltage-gated sodium-channels. By suppressing the release of glutamate and aspartate, lamotrigine acts as a membrane stabilizer, and it is also effective in bipolar disorder and migraine. However, lamotrigine is known to induce tremor among 4-10% of patients. We examined the lamotrigine-induced tremor in 28 epilepsy patients (age: 38.06 ± 13.56 years; 24 females and 4 males) receiving lamotrigine monotherapy and compared the data to 30 age- and sex-matched controls (age: 33.06 ± 10.71 years; 25 females and 5 males). Tremor was visually assessed by clinical tremor rating scales. Quantitative characteristics (intensity, center frequency and frequency dispersion) which are regularly used to differentiate various tremor syndromes were measured by validated, sensitive biaxial accelerometry in resting, postural and intentional positions. Regularity of repetitive finger and hand movements and reaction time were also determined. Data were statistically analyzed. Clinical tremor rating scales detected pathological tremor in three patients (10%), while accelerometry revealed tremor in seven patients (25%). Center frequency of patients with pathological tremor was similar to controls, but the frequency dispersion was significantly lower and tremor intensity was significantly higher in both postural and intentional positions. Rhythmic movements and reaction time were normal. Our results show that objective measurements detect pathological intention tremor in 25% of epilepsy patients receiving lamotrigine monotherapy. Quantitative characteristics suggest the involvement of the cerebellum in the pathomechanism of lamotrigine-induced tremor. Determining the parameters of drug-induced tremor syndromes might help to understand the complex action of tremor generator networks.
In 1973, rotaviruses A (RVAs) were discovered as major causative agents of acute gastroenteritis in infants and young children worldwide. The infectious RV virion is an icosahedral particle composed of three concentric protein layers surrounding the 11 double-stranded (dsRNA) segments. An in vitro replication system for RVs in permanent cell lines was developed in 1982 and expanded to replication in intestinal organoids in 2015. However, the details of rotavirus (RV) entry into cells and particle maturation mechanisms at the molecular level remain incompletely understood. Slowing down human RVA replication in cell culture on ice allowed morphological visualization of virus particle entry and the assembly of triple-layered particles (virion). Although RVAs are non-enveloped viruses, after virus attachment to the cell membrane, the virus enters the cell by perforating the plasma membrane by a fusion mechanism involving VP5* of the cleaved VP4 protein, as the alternative virus entry route besides the receptor-mediated endocytosis which is generally accepted. After assembling double-layered particles (DLPs) in viroplasm or cytoplasm, they appear to be connected with the endoplasmic reticulum (ER) membrane and become coated with outer capsid proteins (VP4 and VP7) in a coating process. The perforation of the ER membrane is caused by an unknown mechanism following interaction between non-structural protein 4 (NSP4) and the inner capsid protein VP6 of the DLPs. The coating process is closely related to the formation of a hetero-oligomeric complex (NSP4, VP4 and VP7). These lines of evidence suggest the existence of novel mechanisms of RV morphogenesis.